The long-term objective of this research is to relate functional deficits in patients with visual disorders to underlying cellular pathophysiology. The proposed research uses psychophysical measures to develop new methods for evaluation of progression of glaucomatous visual loss, and a quantitative model to relate glaucomatous visual defects to ganglion cell damage. The specific aims are: (1) To develop new stimuli designed to improve sensitivity to progressive ganglion cell damage. Modeling of responses of ganglion cell mosaics to conventional perimetric stimuli indicate that tests for progression of glaucoma could be improved if stimuli were used for which the cortical mechanisms mediating detection combine responses of large numbers of retinal ganglion cells. This aim will develop such stimuli by using dynamic noise masks to isolate mechanisms with large spatial summation areas. (2) To evaluate the clinical potential of these new stimuli by measuring test-retest variability and spatial summation in glaucomatous defects. With conventional perimetry, increase in stimulus size decreases test-retest variability, but also decreases sensitivity to glaucomatous damage. This aim will evaluate the new stimuli developed in specific aim 1, which are hypothesized to minimize test-retest variability while retaining sensitivity to glaucomatous defects. Test-retest and spatial summation data will be gathered in glaucomatous defects in order to find optimal conditions for using these stimuli to detect progression of visual loss. (3) To model sensitivity to these new stimuli in terms of cortical summation of ganglion cell responses in normal and glaucomatous eyes. A quantitative model has been developed of the effects of ganglion cell loss on conventional perimetry, which has demonstrated the need to consider effects of cortical summation of ganglion cell responses. The model will be extended to apply to the new stimuli developed in specific aims 1 and 2. This modeling will help interpret the results of specific aims 1 and 2 in terms of ganglion cell damage, and will guide the development of new perimetric methods. These aims will lay the foundation for development of new forms of perimetry, which will provide more powerful methods of assessing progression and evaluating effects of treatment.